The specific aims of this competing renewal are to continue to seek antiviral drugs and drug delivery systems that will improve the treatment of ocular herpes infections, and to investigate possible underlying mechanisms that may make such treatments less effective. We will study thymidine kinase selective and DNA polymerase selective drugs, alone and in combination, to treat herpes infections of the stroma and herpes iritis without toxicity to the host, and test the anti-inflammatory and antiviral effects of cyclosporine, antiviral drugs, and lipoxygenase inhibitors and leukotriene receptor antagonists, alone and in combination, in conjunction with newly developed drug delivery systems to potentiate penetration into the eye. We will also test drug therapies that may prevent virus reactivation and recurrence of ocular herpetic disease, and investigate the molecular genetics of herpes reactivation. Using a primate model for clinical recurrences, we will determine whether a new drug [5'-ethynyl deoxyuridine (EnDU)] that specifically inhibits viral thymidine kinase and appears to have no effect on the host can prevent or modify recurrences. We will investigate, at the molecular level, the relationship between changes in the axonal transport mechanisms or signals conducted through the axonal transport mechanisms to the neuron cell body and changes in cell body gene expression that may lead to reactivation of latent HSV-1. We will examine the possibility that surgical trauma, possibly neuronal in nature, leads to reactivation of latent herpesvirus and subclinical herpetic disease after penetrating keratoplasty in man, as it does in rabbits. We will also continue to develop and test a new and rapid method of diagnosing recurrent superficial corneal herpesvirus infection which involves an immunologically specific reaction that can be completed in less than one hour. New and powerful methodologies will be employed, including high pressure liquid chromatography-mass spectrometry and various molecular biological techniques, such as northern blotting and antisense mRNAs. The ultimate goal of these studies is to improve our understanding of ocular herpevirus infection and thereby develop and test more specific treatments to cure this devastating and blinding eye disease.